The multidisciplinary Nebraska Center for Nanomedicine (NCN), established in 2008 with Center for Biomedical Research Excellence (COBRE) funding, is building a nationally and internationally recognized program of excellence in nanomedicine that combines broad expertise in material, pharmaceutical and biological sciences driven by innovative research. NCN has completed its original objectives and enhanced Nebraska's biomedical research capacity by creating a strategically linked infrastructure of strong collaborative research programs and by mentoring a cadre of talented junior faculty to independent success. 26 NCN members (all COBRE key personnel) have a total of 292 publications (including 86 by mentored junior faculty), 99 new patent applications along with 46 grants (16 related to nanomedicine). This NCN COBRE continuation proposal details our plan to continue building and to sustain a biomedical research center of national prominence and international recognition. The specific aims that move the NCN toward these goals over the next five years are: 1) continue to expand existing research strengths through the support of five thematically linked projects and mentorship of junior faculty into independent investigators; 2) grow research capacity through the pilot project program and the support of innovative projects by experienced researchers with a focus on expanding translational capabilities and clinical research collaborations; 3) continue targeted faculty recruitment to broaden the scope and expertise in the area of nanomedicine research; and 4) sustain the support of essential scientific core facilities, which serve as platforms to increase the capacity f NCN members to compete successfully for NIH funding. The realization of these aims will allow the NCN to emerge from Phase II funding as self-sustaining center of research excellence in nanomedicine, with an increased capacity to pursue programmatic support through individual and multi-investigator, program-wide research grants. Through the development and clinical translation of effective nanomedicines for diagnosis and therapy for human diseases, the NCN will ultimately provide significant benefits for the health of Nebraskans and society at large.